Abstract
Irradiation by light emitting diode (LED) promotes fibroblast proliferation and wound healing. However, its mechanism is still unknown. The purpose of this study was to clarify the mechanism of fibroblast proliferation by LED irradiation. Cultured NIH3T3 fibroblasts from normal mice were irradiated by LED with a center wavelength of 627 nm. LED irradiation was performed with an energy density of 4 J/cm2, at subculture and 24 h later. The expression of several growth factors and their receptors was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR): platelet-derived growth factor (PDGF)-A, PDGF-B, and PDGF-C, transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), PDGF-α receptor, and TGF-β receptor. Then, the activation of the extracellular signal-regulated kinase (ERK) pathway was examined by Western blotting with and without the PDGF receptor inhibitor. LED irradiation induced cell growth of NIH3T3 fibroblasts. The expression of PDGF-C had significantly increased in the irradiated group (P < 0.01). Although strong activation of the ERK pathway was observed in the irradiated group, its activation was completely suppressed by the PDGF receptor inhibitor. We concluded that LED irradiation promotes fibroblast proliferation by increasing autocrine production of PDGF-C and activating the ERK pathway through phosphorylation of the PDGF receptor.
Similar content being viewed by others
References
Whelan HT, Smits RL Jr, Buchman EV, Whelan NT, Turner SG, Margolis DA, Cevenini V, Stinson H, Ignatius R, Martin T, Cwiklinski J, Philippi AF, Graf WR, Hodgson B, Gould L, Kane M, Chen G, Caviness J (2001) Effect of NASA light-emitting diode irradiation on wound healing. J Clin Laser Med Surg 19:305–314
Posten W, Wrone DA, Dover JS, Arndt KA, Silapunt S, Alam M (2005) Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg 31:334–340
Pereira AN, Eduardo Cde P, Matson E, Marques MM (2002) Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 31:263–267
Houreld NN, Abrahamse H (2008) Laser light influences cellular viability and proliferation in diabetic-wounded fibroblast cells in a dose- and wavelength-dependent manner. Lasers Med Sci 23:11–18
Desmet KD, Paz DA, Corry JJ, Eells JT, Wong-Riley MT, Henry MM, Buchmann EV, Connelly MP, Dovi JV, Liang HL, Henshel DS, Yeager RL, Millsap DS, Lim J, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT (2006) Clinical and experimental applications of NIR-LED photobiomodulation. Photomed Laser Surg 24:121–128
Weiss RA, McDaniel DH, Geronemus RG, Weiss MA, Beasley KL, Munavalli GM, Bellew SG (2005) Clinical experience with light-emitting diode (LED) photomodulation. Dermatol Surg 31:1199–1205
DeLand MM, Weiss RA, McDaniel DH, Geronemus RG (2007) Treatment of radiation-induced dermatitis with light-emitting diode (LED) photomodulation. Lasers Surg Med 39:164–168
Kochman AB, Carnegie DH, Burke TJ (2002) Symptomatic reversal of peripheral neuropathy in patients with diabetes. J Am Podiatr Med Assoc 92:125–130
Corazza AV, Jorge J, Kurachi C, Bagnato VS (2007) Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg 25:102–106
Vinck EM, Cagnie BJ, Cornelissen MJ, Declercq HA, Cambier DC (2003) Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation. Lasers Med Sci 18:95–99
Tada K, Ikeda K, Tomita K (2009) Effect of polarized light emitting diode irradiation on wound healing. J Trauma 67:1073–1079
Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT (2004) Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. Mitochondrion 4:559–567
Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B 49:1–17
Shefer G, Oron U, Irintchev A, Wernig A, Halevy O (2001) Skeletal muscle cell activation by low-energy laser irradiation: a role for the MAPK/ERK pathway. J Cell Physiol 187:73–80
Yu W, Naim JO, Lanzafame RJ (1994) The effect of laser irradiation on the release of bFGF from 3T3 fibroblasts. Photochem Photobiol 59:167–170
Yu W, Naim JO, Lanzafame RJ (1994) Expression of growth factors in early wound healing in rat skin. Lasers Surg Med 15:281–289
Vladimirov YA, Osipov AN, Klebanov GI (2004) Photobiological principles of therapeutic applications of laser radiation. Biochemistry (Mosc) 69:103–113
Samoilova KA, Bogacheva ON, Obolenskaya KD, Blinova MI, Kalmykova NV, Kuzminikh EV (2004) Enhancement of the blood growth promoting activity after exposure of volunteers to visible and infrared polarized light. Part I: stimulation of human keratinocyte proliferation in vitro. Photochem Photobiol Sci 3:96–101
Zhang Y, Song S, Fong CC, Tsang CH, Yang Z, Yang M (2003) cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light. J Invest Dermatol 120:849–857
Li X, Pontén A, Aase K, Karlsson L, Abramsson A, Uutela M, Bäckström G, Hellström M, Boström H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U (2000) PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol 2:302–309
Li X, Eriksson U (2003) Novel PDGF family members: PDGF-C and PDGF-D. Cytokine Growth Factor Rev 14:91–98
Reigstad LJ, Varhaug JE, Lillehaug JR (2005) Structural and functional specificities of PDGF-C and PDGF-D, the novel members of the platelet-derived growth factors family. FEBS J 272:5723–5741
Gilbertson DG, Duff ME, West JW, Kelly JD, Sheppard PO, Hofstrand PD, Gao Z, Shoemaker K, Bukowski TR, Moore M, Feldhaus AL, Humes JM, Palmer TE, Hart CE (2001) Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. J Biol Chem 276:27406–27414
Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912
Robinson MJ, Cobb MH (1997) Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9:180–186
Garrington T, Johnson GL (1999) Organization and regulation of mitogen-activated protein kinase signaling pathway. Curr Opin Cell Biol 11:211–218
Midgley VC, Khachigian LM (2004) Fibroblast growth factor-2 induction of platelet-derived growth factor-C chain transcription in vascular smooth muscle cells is ERK-dependent but not JNK-dependent and mediated by Egr-1. J Biol Chem 279:40289–40295
Kovalenko M, Gazit A, Böhmer A, Rorsman C, Rönnstrand L, Heldin CH, Waltenberger J, Böhmer FD, Levitzki A (1994) Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer Res 54:6106–6114
Kovalenko M, Rönnstrand L, Heldin CH, Loubtchenkov M, Gazit A, Levitzki A, Böhmer FD (1997) Phosphorylation site-specific inhibition of platelet-derived growth factor beta-receptor autophosphorylation by the receptor blocking tyrphostin AG1296. Biochemistry 36:6260–6269
Canalis E, Raisz LG (1980) Effect of fibroblast growth factor on cultured fetal rat calvaria. Metabolism 29:108–114
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Komine, N., Ikeda, K., Tada, K. et al. Activation of the extracellular signal-regulated kinase signal pathway by light emitting diode irradiation. Lasers Med Sci 25, 531–537 (2010). https://doi.org/10.1007/s10103-009-0743-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10103-009-0743-7